Chemical Constituents from Two Vitex Medicinal Plants and their Bioactivities

The Verbenaceae family consists of ca. 100 genera and 2600 species; of pantropical distribution, only a limited number of species occur in temperate regions. The largest genera are Clerodendrum (400 species), Vitex (250 species), Verbena (250 species), Lippia (200 species), Premma (200 species), and Lantana (150 species). In this family, one of the best sources of bioactive natural products is Vitex, a genus of shrubs and small trees with different medicinal uses in folk medicine, found in tropical and subtropical regions.

Our studies were undertaken to isolate and characterize the active constituents and to ascertain the bioactivities of two Vitex species in China (V. rotundifolia and V. negundo). From V. rotundifolia fruits, thirteen compounds were isolated and identified, among which flavonoids were found to be the major constituents, including casticin, artemitin, luteolin and 5, 7, 2', 5'-tetrahydroxyflavone. Studying anti-PMS (premenstrual syndrome) activities of V. rotundifolia fruits, we found that its major component, casticin (flavonoid), signifianctly inhibited prolactin release both in vivo and in vitro. At the same time, casticin has potent analgesic and anti-inflammatory properties that can play an important role in treating PMS. In addition, two other constituents, rotundifuran (diterpene) and agnuside (iriod glucoside) exhibited estrogen-like effects via the estrogen response pathway through interaction with the estrogen receptor, progesterone receptor and pS2. This supports the notion that V. rotundifolia fruits exerts its effects through multiple and synergistic mechanisms due to different bioactive chemical groups in the treatment of PMS. Bioactivity-guided fractionation of V. negundo fruits assigned the dichloromethane- and acetoacetate-soluble parts to be the active fractions of antiinflammation, which were comprised of a great amount of lignans and terpenoids. A total of 79 compounds were isolated and identified from these active fractions, including 9 new lignans, 10 new diterpenes and 2 novel nortriterpenes, as well as 30 known compounds isolated from this plant for the first time. A productive phenylnaphthalene-type lignan, 6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydroxymethyl-7-methoxy-3, 4-dihydro-2-naphthaldehyde, was proven to be the active compound with anti-inflammatory activity both in vivo and in vitro. Phenylnaphthalene-type lignans were found to be the principal anti-inflammatory constituents in V. negundo fruits.